ArticleCell2019
Lactate Is a Natural Suppressor of RLR Signaling by Targeting MAVS.
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Article in Cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 353 papers.
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353citing papers in PubMed
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353 citing papers in PubMed, 567 citations in OpenAlex.
- Article
- Lactylation in influenza a virus infection: Current evidence, knowledge gaps, and future perspectives.Virulence · 2026Review
- Lactate Signal: Modulator of Cellular Energy Production and Anabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Lactate metabolism and protein lactylation in inflammatory and tumor microenvironments.Molecular biomedicine · 2026Review
- Lactylation of its phosphoprotein interferes with the replication of the spring viremia of carp virus.Microbiology spectrum · 2026Article
- Review
- Restricted MHC-II trafficking inbioRxiv : the preprint server for biology · 2026Article
- Tetherin enforces an immunometabolic checkpoint that coordinates glycolytic and interferon signaling in adipocytes.bioRxiv : the preprint server for biology · 2026Article
- pH-neutralization strategy to suppress GPCR68 spatiotemporally activates T cells and enhances anti-tumor immunity.Bioactive materials · 2026Article
- Topical Glycolysis Inhibition Restores MAVS-Associated Antiviral Signaling in Herpes Simplex Keratitis.Investigative ophthalmology & visual science · 2026Article
- Harnessing the glycolysis-TCA cycle axis to boost host defense against neonatal infection.EMBO molecular medicine · 2026Article
- Lactate in ruminant health: metabolic roles and the emerging significance of lactylation.Journal of animal science and biotechnology · 2026Review
- Pestivirus bovine viral diarrhea virus infection induces ROS-HIF-1a axis-driven glycolytic reprogramming, which increases viral replication by impairing RIG-I-dependent type I interferon response.Journal of virology · 2026Article
- Review
- Metabolites as signalling molecules in the tumour immune microenvironment.Nature reviews. Immunology · 2026Review
- The activation of the metabolic oxaloacetate-pyruvate axis restores influenza A virus replication during impaired glycolysis.Virology journal · 2026Article
- Lactate and lactylation: mechanisms, function, diseases, and therapeutic targets.Molecular biomedicine · 2026Review
- TGFβ primes alveolar-like macrophages to induce type I IFN following TLR2 activation.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Metabolic pattern changes of macrophages during cancer development and progression.Journal of translational medicine · 2026Review
- Glycolysis inhibition in tuberculosis-driven metabolic rewiring reduces HIV-1 spread in macrophages.Life science alliance · 2026Article
293 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors at 5 institutions in 3 countries.
Weina ZhangState Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis; State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, National Center of Biomedical Analysis, Beijing, Beijing 100850, China; Department of Cancer Biology, Wake Forest Baptist Medical Center, Wake Forest University, Winston Salem, NC 27101, USA.
Guihua WangDepartment of Cancer Biology, Wake Forest Baptist Medical Center, Wake Forest University, Winston Salem, NC 27101, USA; Department of Gastrointestinal Surgery Center and Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Zhi-Gang XuInternational Academy of Targeted Therapeutics and Innovation, Chongqing University of Arts and Sciences, Chongqing 402160, China.
Haiqing TuState Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis; State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, National Center of Biomedical Analysis, Beijing, Beijing 100850, China.
Fuqing HuDepartment of Gastrointestinal Surgery Center and Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Jiang DaiState Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis; State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, National Center of Biomedical Analysis, Beijing, Beijing 100850, China.
Yan ChangState Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis; State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, National Center of Biomedical Analysis, Beijing, Beijing 100850, China.
Yaqi ChenDepartment of Gastrointestinal Surgery Center and Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Yanjun LuDepartment of Gastrointestinal Surgery Center and Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Haolong ZengDepartment of Gastrointestinal Surgery Center and Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Zhen CaiDepartment of Cancer Biology, Wake Forest Baptist Medical Center, Wake Forest University, Winston Salem, NC 27101, USA.
Fei HanDepartment of Cancer Biology, Wake Forest Baptist Medical Center, Wake Forest University, Winston Salem, NC 27101, USA.
Chuan XuDepartment of Cancer Biology, Wake Forest Baptist Medical Center, Wake Forest University, Winston Salem, NC 27101, USA.
Guoxiang JinDepartment of Cancer Biology, Wake Forest Baptist Medical Center, Wake Forest University, Winston Salem, NC 27101, USA.
Li SunDepartment of Cancer Biology, Wake Forest Baptist Medical Center, Wake Forest University, Winston Salem, NC 27101, USA.
Bo-Syong PanDepartment of Cancer Biology, Wake Forest Baptist Medical Center, Wake Forest University, Winston Salem, NC 27101, USA.
Shiue-Wei LaiDepartment of Cancer Biology, Wake Forest Baptist Medical Center, Wake Forest University, Winston Salem, NC 27101, USA.
Che-Chia HsuDepartment of Cancer Biology, Wake Forest Baptist Medical Center, Wake Forest University, Winston Salem, NC 27101, USA.
Jia XuInternational Academy of Targeted Therapeutics and Innovation, Chongqing University of Arts and Sciences, Chongqing 402160, China.
Zhong-Zhu ChenInternational Academy of Targeted Therapeutics and Innovation, Chongqing University of Arts and Sciences, Chongqing 402160, China.
Hong-Yu LiUniversity of Arkansas for Medical Sciences, College of Pharmacy, Division of Pharmaceutical Science, 200 South Cedar, Little Rock, AR 72202, USA.
Pankaj SethDepartment of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Junbo HuDepartment of Gastrointestinal Surgery Center and Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Xuemin ZhangState Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis; State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, National Center of Biomedical Analysis, Beijing, Beijing 100850, China.
Huiyan LiState Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis; State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, National Center of Biomedical Analysis, Beijing, Beijing 100850, China.
Hui-Kuan LinDepartment of Cancer Biology, Wake Forest Baptist Medical Center, Wake Forest University, Winston Salem, NC 27101, USA; Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan. Electronic address: hulin@wakehealth.edu.
Atrium Health Wake Forest Baptist · USNational Center of Biomedical Analysis · CNTongji Hospital · CNChongqing University of Arts and Sciences · CNBeth Israel Deaconess Medical Center · US
Funding
Tumor Tissue CoreP30CA012197 · NCI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI Ruben A. Mesa · 1985 to 2026
$55.4MIdentification of a new strategy for cancer therapyR01CA193813 · NCI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI LIN, HUI-KUAN · 2015 to 2019
$1.8MNovel posttranslational modification in LKB1 activation and cancer developmentR01CA182424 · NCI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI LIN, HUI-KUAN · 2014 to 2018
$1.6MSelective RET Kinase and Its Mutant Inhibitors for the Treatment of Medullary Thyroid CancerR01CA197178 · NCI · UNIV OF ARKANSAS FOR MED SCIS · PI LI, HONG-YU, MCDONALD, NEIL · 2015 to 2019
$1.5MDiscovery and Development of a Selective pan-FLT3-ITD Kinase Inhibitor Clinical Candidate for the Treatment of FLT3-ITD-Driven AMLR01CA194094 · NCI · UNIV OF ARKANSAS FOR MED SCIS · PI LI, HONG-YU, SHAH, NEIL P · 2015 to 2018
$1.5MNCI NIH HHS P30 CA012197NCI NIH HHS R01 CA182424NCI NIH HHS R01 CA193813NCI NIH HHS R01 CA194094NCI NIH HHS R01 CA197178
Abstract
RLR-mediated type I IFN production plays a pivotal role in elevating host immunity for viral clearance and cancer immune surveillance. Here, we report that glycolysis, which is inactivated during RLR activation, serves as a barrier to impede type I IFN production upon RLR activation. RLR-triggered MAVS-RIG-I recognition hijacks hexokinase binding to MAVS, leading to the impairment of hexokinase mitochondria localization and activation. Lactate serves as a key metabolite responsible for glycolysis-mediated RLR signaling inhibition by directly binding to MAVS transmembrane (TM) domain and preventing MAVS aggregation. Notably, lactate restoration reverses increased IFN production caused by lactate deficiency. Using pharmacological and genetic approaches, we show that lactate reduction by lactate dehydrogenase A (LDHA) inactivation heightens type I IFN production to protect mice from viral infection. Our study establishes a critical role of glycolysis-derived lactate in limiting RLR signaling and identifies MAVS as a direct sensor of lactate, which functions to connect energy metabolism and innate immunity.
Indexed as
Adaptor Proteins, Signal TransducingAnimalsDEAD Box Protein 58FemaleGlycolysisHEK293 CellsHumansInterferon-betaLactic AcidL-Lactate DehydrogenaseMaleMiceMice, Inbred C57BLMice, TransgenicRAW 264.7 CellsReceptors, Cell SurfaceAdaptor Proteins, Signal TransducingDEAD Box Protein 58Interferon-betaLactic AcidLDHA protein, humanL-Lactate DehydrogenaseMAVS protein, humanMAVS protein, mouseReceptors, Cell SurfaceReceptors, ImmunologicRIGI protein, humanRobo3 protein, mouseRoundabout Proteinsglucose metabolisminterferonlactateMAVSRLR signaling
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